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Mutations in the insulin receptor (INSR) gene underlie rare severe INSR-related insulin resistance syndromes (SIR), including insulin resistance type A, Rabson⁻Mendenhall syndrome and Donohue syndrome (DS), with DS representing the most severe form of insulin resistance. Treatment of these cases is challenging, with the majority of DS patients dying within the first two years of life. rhIGF-I (mecasermin) has been reported to improve metabolic control and increase lifespan in DS patients. A case report and literature review were completed. We present a case involving a male patient with DS, harbouring a homozygous mutation in the INSR gene (c.591delC). Initial rhIGF-I application via BID (twice daily) injection was unsatisfactory, but continuous subcutaneous rhIGF-I infusion via an insulin pump improved weight development and diabetes control (HbA1c decreased from 10 to 7.6%). However, our patient died at 22 months of age during the course of a respiratory infection in in Libya. Currently available data in the literature comprising more than 30 treated patients worldwide seem to support a trial of rhIGF-I in SIR. rhIGF-I represents a treatment option for challenging SIR cases, but careful consideration of the therapeutic benefits and the burden of the disease is warranted. Continuous application via pump might be advantageous compared to single injections.

Objective: Insulin dose-adjusted hemoglobin A1c (HbA1C, IDAA1c) correlates well with stimulated C-peptide levels, but has not yet been evaluated in a large cohort of patients with Type 1 diabetes (T1D)., Methods: We investigated prevalence of partial remission (PREM) defined by IDAA1c ≤9 in 3657 in children with new-onset T1D who were continuously followed over 6 years. We evaluated the predictors of PREM using the multicenter database from the DPV (Diabetes Patienten Verlaufsdokumentation) registry., Results: PREM occurred in 71% of patients. Median duration was 9 (0-21) months. Compared to children <5 years at T1D onset, those aged 5-10 and ≥10 years had twice the chance of developing PREM (OR: 2.08, CI: 1.67-2.60; P < .001 and OR: 2.16, CI: 1.70-2.75; P < .001). Boys were more likely to develop PREM than girls (OR 1.41, CI: 1.18-1.69; P = .0002). Further predictors for PREM were: ketoacidosis, autoantibodies, and HbA1c at T1D onset. These results were confirmed by quantile regression analysis with duration of PREM as dependent variable., Conclusion: This research on a large cohort provides insight into epidemiologic characteristics of PREM in T1D defined by IDAA1c. As IDAA1c does not discriminate between insulin sensitivity and secretion, available data cannot resolve whether the sex-difference in PREM reflects innate higher insulin resistance in girls, or better beta-cell recovery in boys. Further research is needed to clarify the usefulness and performance of IDAA1c in clinical practice., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To investigate changes in diabetes treatment over the last two decades in three age-groups of children and adolescents with type 1 diabetes (T1D) from Germany and Austria., Methods: 63,967 subjects (<18yr) with T1D documented between 1995 and 2014 from the DPV-database were included and stratified according to age (0.5-<6, 6-<12, 12-<18yr). Regression models were applied for insulin regimens (<3 and ≥4 injection time points/day, or continuous subcutaneous insulin infusion (CSII)), use of rapid- and long acting insulin analogues, NPH insulin, and frequency of self-monitoring of blood glucose (SMBG)/day. Models were adjusted for sex, diabetes duration, and migration background. P-value for trend was given., Findings: The number of subjects with <3 injection time points/day decreased from 1995 to 2014 to <5% in all age-groups (p<0.0001). Proportion of patients with ≥4 injections/day increased until the early 2000s, and then declined until 2014. This trend was not found in 6-<12yr olds (p = 0.3403). CSII increased in all age-groups (p<0.0001) with the highest increase in children <6 years (from 0.4% to 79.2%), and the lowest increase in 12-<18 year olds (from 1.0% to 38.9%). NPH insulin decreased in all age-groups (p<0.0001). Insulin analogues, especially rapid-acting, became more frequent in all age-groups (p<0.0001), accounting for 78.4% in 2014 for all subjects. The highest use was found in the youngest children (in 2014: 85.6%), the lowest use in 6-<12 year olds (in 2014: 72.9%). The number of SMBG/day increased from 2.2 to 6.4 with a similar rise in all age-groups (p<0.0001). Frequency was highest in subjects <6yr., Conclusions: In all age-groups, T1D treatment was intensified over the last 20 years. Age-specific differences in trends were particularly observed in the number of patients on CSII, in the number of patients with 4 or more injections/day, and in the frequency of SMBG/day.